It’s human instinct to want to destroy cancer as fast as possible.
“Cancer is this bug. You just want to slash it, rip it out or attack it like an enemy target,” said Benjamin Zeskind, co-founder, CEO and president of Immuneering Corporation.
But while an aggressive approach may seem intuitive, it can sometimes backfire. Research shows that harsh, sustained attacks on tumors may accelerate the development of dangerous mutations, Zeskind said. To overcome that hurdle, Immuneering is testing an approach that slows cancer down rather than rushing to destroy it.
This slow and steady concept gained more validation in June when the company announced early but promising data from a phase 2 trial of its MEK inhibitor atebimetinib combined with chemotherapy, which showed a six-month 94% overall survival in pancreatic cancer. The results marked a major step for a disease with a 67% six-month survival rate using standard chemotherapies. Whether the results — and Immuneering’s approach — will hold up in a pivotal trial planned for 2026 remains to be seen.
“Everyone's focused on killing the tumor and the goal should really be to prevent the tumor from killing the patient,” Zeskind said. “And if you can do that, cancer becomes a chronic, manageable disease, like diabetes, cardiac disease or HIV. I think we have to control cancer before we cure it.”
Closing a main cancer pathway
MEK inhibitors target key proteins in the mitogen-activated protein kinase pathway, a cancer superhighway that fuels tumor growth in up to one-third of all cancers. The broad mechanism allows them to target multiple tumor types, including those with RAS mutations, which are common in melanoma, pancreatic, colorectal and lung cancers.
The FDA approved the first MEK inhibitor, a melanoma drug from Novartis, in 2013. It’s now also approved alone or in combination with Tafinlar (a BRAF inhibitor) for pediatric low-grade glioma brain tumors, and for several other oncology indications. More MEK drugs approvals followed for Genentech, SpringWorks Therapeutics and AstraZeneca.
“There’s this no pain, no gain philosophy that we think is outdated.”
Benjamin Zeskind
Co-founder, CEO and president of Immuneering Corporation
The MEK pipeline now includes an ovarian cancer candidate from Verastem Oncology and potential new indications for existing drugs, such as SpringWorks’ mirdametinib, which is in phase 2 testing for low-grade glioma.
One downside for MEK inhibitors, however, is that patients eventually encounter resistance and a range of side effects.
Some companies are trying combination approaches or time-on-time-off dosing schedules to overcome resistance. Immuneering is testing a unique dosing strategy, built on earlier work in evolutionary oncology from scientists such as Dr. Robert Gatenby at Moffitt Cancer Center.
While most MEK drugs continuously block the MAPK pathway, Immuneering’s drug is designed to shut it down for a short time to damage cancerous cells, and then reopen it to minimize harm to healthy cells. This strategy aims to minimize debilitating side effects for patients while maintaining efficacy.
“There’s this no pain, no gain philosophy that we think is outdated,” Zeskind said. “If it’s a design goal from the start you can make cancer drugs that don’t make patients feel terrible all the time.”
The only grade three or higher side effects in the atebimetinib trial were anemia and neutropenia.
“And these are things associated with the chemotherapy that we're combining with,” he said.
This intermittent high-dose, fast-clearance approach also keeps tumors off balance, disrupting the natural selection process that drives drug resistance. Because mutations can occur in as little as 24 hours, Immuneering designed a drug that delivers a high daily dose of medication and clears rapidly within the same day.
Modifying drug dosing
The phase 2 trial for atebimetinib also saw a 72% progression-free survival at six months, compared with 44% for the standard of care. The trial hasn’t reached median overall or progression-free survival. Results were encouraging and seemed to build over time, Zeskind said.
“We're seeing patients where it's very slow for months and months, 10%, 20%, and then the tumors just start collapsing. They drop from 20% down to 60%,” Zeskind said.
Some results were dramatic.
“We've had multiple patients where specific lesions basically became undetectable,” he said. “We shared a case study of a patient with two liver lesions that shrank over the course of four scans to the point that they were no longer detectable. Gone. That doesn't happen in pancreatic cancer.”
Based on these data, the company is looking ahead to determine what other cancer types they will target with this broad-action drug.
The hope is that the approach will not only help patients but also change the way people think about cancer treatment.
“You don't need to outsmart cancer,” Zeskind said. “You don't need to kill the cancer. You just need to outpace it.”
